17,20-lyase deficiency, isolated

Summary

17,20-lyase deficiency, isolated (MONDO:0800378) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 2
• Phenotypes (HPO): 36

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		15	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

36 HPO clinical features (Orphanet curated; top 36 by frequency):

HPO ID	Term	Frequency
HP:0000013	Hypoplasia of the uterus	Very frequent (80-99%)
HP:0000047	Hypospadias	Very frequent (80-99%)
HP:0000054	Micropenis	Very frequent (80-99%)
HP:0000144	Decreased fertility	Very frequent (80-99%)
HP:0000147	Polycystic ovaries	Very frequent (80-99%)
HP:0000786	Primary amenorrhea	Very frequent (80-99%)
HP:0000815	Hypergonadotropic hypogonadism	Very frequent (80-99%)
HP:0000823	Delayed puberty	Very frequent (80-99%)
HP:0000939	Osteoporosis	Very frequent (80-99%)
HP:0002215	Sparse axillary hair	Very frequent (80-99%)
HP:0002225	Sparse pubic hair	Very frequent (80-99%)
HP:0002231	Sparse body hair	Very frequent (80-99%)
HP:0002750	Delayed skeletal maturation	Very frequent (80-99%)
HP:0004349	Reduced bone mineral density	Very frequent (80-99%)
HP:0008187	Absence of secondary sex characteristics	Very frequent (80-99%)
HP:0008193	Primary gonadal insufficiency	Very frequent (80-99%)
HP:0008214	Decreased serum estradiol	Very frequent (80-99%)
HP:0008232	Elevated circulating follicle stimulating hormone level	Very frequent (80-99%)
HP:0008675	Enlarged polycystic ovaries	Very frequent (80-99%)
HP:0011969	Elevated circulating luteinizing hormone level	Very frequent (80-99%)
HP:0012112	Abnormality of circulating corticosterone level	Very frequent (80-99%)
HP:0030349	Decreased circulating androgen level	Very frequent (80-99%)
HP:0040171	Decreased serum testosterone concentration	Very frequent (80-99%)
HP:0100607	Dysmenorrhea	Very frequent (80-99%)
HP:0000028	Cryptorchidism	Frequent (30-79%)
HP:0000868	Decreased fertility in females	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0008726	Hypoplasia of the vagina	Frequent (30-79%)
HP:0008734	Decreased testicular size	Frequent (30-79%)
HP:0012041	Decreased fertility in males	Frequent (30-79%)
HP:0000033	Ambiguous genitalia, male	Occasional (5-29%)
HP:0000037	Male pseudohermaphroditism	Occasional (5-29%)
HP:0000771	Gynecomastia	Occasional (5-29%)
HP:0001508	Failure to thrive	Occasional (5-29%)
HP:0008730	Female external genitalia in individual with 46,XY karyotype	Occasional (5-29%)
HP:0012244	Abnormal sex determination	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	17,20-lyase deficiency, isolated
Mondo ID	MONDO:0800378
Orphanet	90796
UMLS	C3277849
MedGen	479479
GARD	0028052
Is cancer (heuristic)	no

Data availability: 2 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › endocrine system disorder › 17,20-lyase deficiency, isolated

Related subtypes (47): autoimmune disorder of endocrine system, parathyroid gland disorder, endocrine gland neoplasm, gonadal disorder, pancreas disorder, thyroid gland disorder, pituitary gland disorder, thymus gland disorder, liver disorder, adrenal gland disorder, hyperinsulinemic hypoglycemia, non-neoplastic bile duct disorder, endocrine tuberculosis, campomelic dysplasia, polycystic ovary syndrome, dilated cardiomyopathy-hypergonadotropic hypogonadism syndrome, hypohidrotic ectodermal dysplasia-hypothyroidism-ciliary dyskinesia syndrome, genito-palato-cardiac syndrome, hypoinsulinemic hypoglycemia and body hemihypertrophy, Bamforth-Lazarus syndrome, blepharophimosis - intellectual disability syndrome, SBBYS type, Wolfram-like syndrome, hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism, estrogen resistance syndrome, short stature, microcephaly, and endocrine dysfunction, polyendocrinopathy, pituitary deficiency, hereditary endocrine growth disease, diencephalic syndrome, muscular pseudohypertrophy-hypothyroidism syndrome, neonatal iodine exposure, disorders of vitamin D metabolism, rapid-onset childhood obesity-hypothalamic dysfunction-hypoventilation-autonomic dysregulation syndrome, duplication of the pituitary gland, familial hypocalciuric hypercalcemia, hypothalamic adipsic hypernatraemia syndrome, Leydig cell hypoplasia, inherited obesity, beta thalassemia, thyroid hormone metabolism, abnormal, neuroendocrine disorder, NKX2-1 related choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction, parneoplastic endocrine syndrome, 17-alpha-hydroxylase/17,20-lyase deficiency, combined complete, 17-alpha-hydroxylase/17,20-lyase deficiency, combined partial, disorder of GNAS inactivation, acquired hypothalamic obesity

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

2 retrieved; paginated sample, class counts are floors:

1 pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1787	NM_000102.4(CYP17A1):c.1040G>A (p.Arg347His)	CYP17A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1788	NM_000102.4(CYP17A1):c.1073G>A (p.Arg358Gln)	CYP17A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CYP17A1	Orphanet:90793	Congenital adrenal hyperplasia due to 17-alpha-hydroxylase deficiency
CYP17A1	Orphanet:90796	46,XY difference of sex development due to isolated 17,20-lyase deficiency

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CYP17A1	HGNC:2593	ENSG00000148795	P05093	Steroid 17-alpha-hydroxylase/17,20 lyase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CYP17A1	Steroid 17-alpha-hydroxylase/17,20 lyase	A cytochrome P450 monooxygenase involved in corticoid and androgen biosynthesis.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CYP17A1	Enzyme (other)	yes	1.14.14.19	Cyt_P450, Cyt_P450_E_grp-I, Cyt_P450_CS

Expression context

Cohort genes with no expression data: 0.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left adrenal gland	1
right adrenal gland	1
right adrenal gland cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CYP17A1	165	tissue_specific	yes	right adrenal gland, right adrenal gland cortex, left adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CYP17A1	2,720

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CYP17A1	P05093	17

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective CYP17A1 causes AH5	1	11420.0×	3e-04	CYP17A1
Androgen biosynthesis	1	1038.2×	0.001	CYP17A1
Glucocorticoid biosynthesis	1	878.5×	0.001	CYP17A1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cortisol biosynthetic process	1	2106.5×	0.001	CYP17A1
androgen biosynthetic process	1	1872.4×	0.001	CYP17A1
progesterone metabolic process	1	1685.2×	0.001	CYP17A1
glucocorticoid biosynthetic process	1	1532.0×	0.001	CYP17A1
hormone biosynthetic process	1	1404.3×	0.001	CYP17A1
sex differentiation	1	842.6×	0.002	CYP17A1
steroid biosynthetic process	1	601.9×	0.002	CYP17A1
steroid metabolic process	1	337.0×	0.003	CYP17A1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
CYP17A1	CLOTRIMAZOLE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CYP17A1	16	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CLOTRIMAZOLE	4	CYP17A1
TESTOSTERONE PROPIONATE	4	CYP17A1
TIOCONAZOLE	4	CYP17A1
POSACONAZOLE	4	CYP17A1
KETOCONAZOLE	4	CYP17A1
ISOCONAZOLE	4	CYP17A1
ABIRATERONE	4	CYP17A1
ABIRATERONE ACETATE	4	CYP17A1
BIFONAZOLE	4	CYP17A1
OSILODROSTAT	4	CYP17A1
AMINOGLUTETHIMIDE	4	CYP17A1
ECONAZOLE	4	CYP17A1
MICONAZOLE	4	CYP17A1
ORTERONEL	3	CYP17A1
GALETERONE	3	CYP17A1
AZALANSTAT	2	CYP17A1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
CYP17A1	239	Binding:198, ADMET:37, Functional:4

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CYP17A1	1.14.14.19, 1.14.14.32	steroid 17alpha-monooxygenase, 17alpha-hydroxyprogesterone deacetylase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
CYP17A1	239

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

16 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
CLOTRIMAZOLE	4	CYP17A1
TESTOSTERONE PROPIONATE	4	CYP17A1
TIOCONAZOLE	4	CYP17A1
POSACONAZOLE	4	CYP17A1
KETOCONAZOLE	4	CYP17A1
ISOCONAZOLE	4	CYP17A1
ABIRATERONE	4	CYP17A1
ABIRATERONE ACETATE	4	CYP17A1
BIFONAZOLE	4	CYP17A1
OSILODROSTAT	4	CYP17A1
AMINOGLUTETHIMIDE	4	CYP17A1
ECONAZOLE	4	CYP17A1
MICONAZOLE	4	CYP17A1
ORTERONEL	3	CYP17A1
GALETERONE	3	CYP17A1
AZALANSTAT	2	CYP17A1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CYP17A1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.